2,2-dichloropropanoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-methyl-N-[2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenyl]hydroxyamine (500 mg, 1.38 mmol) in methylene chloride (2 ml) is added pyridine (0.16 ml, 2.00 mmol) and benzene (3 ml), followed by α,α-dichloropropionyl chloride (328 mg, 1.5 eq.). The mixture is stirred at RT for 2 hours. The resulting reaction mixture is then taken up in methylene chloride, washed, dried and evaporated to dryness. The crude product is purified by prep. TLC to yield N-methyl-N-[2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenyl]-α,α-dichloropropionyloxyamine. nmr (CDCl3) τ7.77(S,3H,COC Cl2CH3), 6.67(S, 3H, NCH3). The resulting reaction mixture washed dried evaporated to dryness The crude product is purified by prep

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction vessel was chrged with 2 g 1-methyl-1,2,3,4-tetrahydroisoquinoline, 10 ml 10% sodium hydroxide and 50 ml methylene chloride. With this mixture stirred, 3 ml 2,2-dichloropropionyl chloride was added dropwise to the mixture. The mixture was stirred for 20 minutes, then water was added. The organic extract was dried with magnesium sulfate, stripped of solvent and subjected to Kugelrohr distillation (170° C. @ 0.25 mm Hg) to provide 2.7 g of a yellow oil product having the elemental analysis reported in Table I. The mixture was stirred for 20 minutes The organic extract was dried with magnesium sulfate subjected to Kugelrohr distillation (170° C. @ 0.25 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-methyl-N-[2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenyl]hydroxyamine (500 mg, 1.38 mmol) in methylene chloride (2 ml) is added pyridine (0.16 ml, 2.00 mmol) and benzene (3 ml), followed by α,α-dichloropropionyl chloride (328 mg, 1.5 eq.). The mixture is stirred at RT for 2 hours. The resulting reaction mixture is then taken up in methylene chloride, washed, dried and evaporated to dryness. The crude product is purified by prep. TLC to yield N-methyl-N-[2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenyl]-α,α-dichloropropionyloxyamine. nmr (CDCl3) τ7.77(S,3H,COC Cl2CH3), 6.67(S, 3H, NCH3). The resulting reaction mixture washed dried evaporated to dryness The crude product is purified by prep

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-methyl-N-[2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenyl]hydroxyamine (500 mg, 1.38 mmol) in methylene chloride (2 ml) is added pyridine (0.16 ml, 2.00 mmol) and benzene (3 ml), followed by α,α-dichloropropionyl chloride (328 mg, 1.5 eq.). The mixture is stirred at RT for 2 hours. The resulting reaction mixture is then taken up in methylene chloride, washed, dried and evaporated to dryness. The crude product is purified by prep. TLC to yield N-methyl-N-[2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenyl]-α,α-dichloropropionyloxyamine. nmr (CDCl3) τ7.77(S,3H,COC Cl2CH3), 6.67(S, 3H, NCH3). The resulting reaction mixture washed dried evaporated to dryness The crude product is purified by prep

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a dry reaction vessel were added L-proline (115 g., 1.0 moles, 1.0 eq.), 144 mL of 6 N sodium hydroxide and 20 g. solid sodium hydroxide. The clear, colorless solution (pH=11.5) was cooled to +10° C. in an ice bath with stirring. All of the above 2,2-dichloropropionyl chloride was diluted with 50 mL methylene chloride and added to the L-proline solution over 2 hours, keeping the solution temperature below +10 ° C. and the pH at 11.5 by simultaneous addition of 290 mL of 6N sodium hydroxide to yield 2,2-dichloropropionyl-L-proline. The pH was adjusted to 3 by the addition of 216 mL of 6N hydrochloric acid. The solid which formed was collected by filtration using 300 mL of 6N hydrochloric acid as a wash to yield white crystalline 2,2-dichloropropionyl-L-proline which was dried under vacuum (30 Torr) for 18 hours to give 216 g. (90% yield based on L-proline). HPLC at 23 minutes showed ≥96% purity. The recrystallization from ethyl acetate or ethyl acetate-hexane removes 0.5 mole of water but does not significantly improve purity. m.p. 61°-62° C. To a dry reaction vessel the solution temperature below +10 ° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a dry reaction vessel were added L-proline (115 g., 1.0 moles, 1.0 eq.), 144 mL of 6 N sodium hydroxide and 20 g. solid sodium hydroxide. The clear, colorless solution (pH=11.5) was cooled to +10° C. in an ice bath with stirring. All of the above 2,2-dichloropropionyl chloride was diluted with 50 mL methylene chloride and added to the L-proline solution over 2 hours, keeping the solution temperature below +10 ° C. and the pH at 11.5 by simultaneous addition of 290 mL of 6N sodium hydroxide to yield 2,2-dichloropropionyl-L-proline. The pH was adjusted to 3 by the addition of 216 mL of 6N hydrochloric acid. The solid which formed was collected by filtration using 300 mL of 6N hydrochloric acid as a wash to yield white crystalline 2,2-dichloropropionyl-L-proline which was dried under vacuum (30 Torr) for 18 hours to give 216 g. (90% yield based on L-proline). HPLC at 23 minutes showed ≥96% purity. The recrystallization from ethyl acetate or ethyl acetate-hexane removes 0.5 mole of water but does not significantly improve purity. m.p. 61°-62° C. To a dry reaction vessel the solution temperature below +10 ° C.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The procedure of Example 1 was followed using 32g (0.2 mole) of 2,2-dichloropropionyl chloride and 44g (0.6 mole) of dimethylformamide and 20g (0.2 mole) of triethylamine. Obtained following distillation was 12g of pure N,N-dimethyl-3,3-dichloro-2-oxobutyramide as a clear, colorless liquid: Bp: 68°-70° (0.2mm); ir (λmax, film) 5.7 (s), 6.1 (s), 7.1 (s), 9.3 (s), 9.9 (s), 12.6 (s) microns. Obtained distillation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution was prepared by admixing 250 milliliters of acetonitrile, 55.3 grams (0.4 mole) of potassium carbonate, 42.5 grams (0.16 mole) of 2-(3,5-dichloro-6-fluoro-2-pyridyloxy)ethanol and 32.3 grams (0.2 mole) of 2,2-dichloropropionyl chloride. This mixture was stirred at room temperature for 4 days. The solids which formed were removed by filtration and the filtrate was concentrated under a reduced pressure. The residual material which remained was dissolved in hexane and washed with water. The hexane was removed under a reduced pressure to yield a pale-orange liquid having a refractive index of n/25D=1.5239. The product was confirmed to be 2-(3,5-dichloro-6-fluoro-2-pyridyloxy)ethyl 2,2-dichloro propionate by its infrared and nuclear magnetic resonance spectrums. A solution was prepared The solids which formed were removed by filtration the filtrate was concentrated under a reduced pressure The residual material which remained was dissolved in hexane washed with water The hexane was removed under a reduced pressure to yield a pale-orange liquid